NDLI: Preventive and therapeutic effects of tacrolimus in an interleukin-10-deficient mouse model of colitis

Content Provider	Springer Nature Link
Author	Okada, Yohei Maeda, riaki Takakura, Shoji Miyata, Keiji Koshiba, Masahiro
Copyright Year	2011
Abstract	To investigate the preventive and therapeutic effects of tacrolimus on colonic inflammation in interleukin-10-deficient (IL-10−/−) mice, which spontaneously develop T-cell-mediated colitis.Tacrolimus or prednisolone, an anti-inflammatory glucocorticoid, was administered to IL-10−/− mice with pre- or post-symptomatic colitis. Effects on colonic inflammation were examined by measuring indices of colitis such as colonic weight/length ratio, cell infiltration, and goblet cell depletion. Effects on cytokine production in colonic lamina propria mononuclear cells (LPMCs) isolated from IL-10−/− mice were also examined.Tacrolimus prevented development of colitis and improved already-developed colitis. Prednisolone prevented the development of colitis, but had no effect on already-developed colitis. Tacrolimus completely inhibited IFN-γ and TNF-α production of activated T-cells in LPMCs, but only partially inhibited IFN-γ, TNF-α, and IL-12 production of activated monocytes/macrophages in LPMCs. Prednisolone inhibited cytokine production in both cell types but exhibited greater potency on monocytes/macrophages than on T-cells.These results suggest that the preventive and therapeutic effect of tacrolimus in IL-10−/− mice colitis might be attributed to the inhibition of colonic T-cell activation rather than monocyte/macrophage activation. T-cell immunosuppression may thus be a promising strategy for treating colonic inflammation.
Starting Page	1049
Ending Page	1059
Page Count	11
File Format	PDF
ISSN	10233830
Journal	Inflammation Research
Volume Number	60
Issue Number	11
e-ISSN	1420908X
Language	English
Publisher	SP Birkhäuser Verlag Basel
Publisher Date	2011-08-10
Publisher Place	Basel
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Inflammatory bowel disease Tacrolimus Interferon-γ Tumour necrosis factor-α Interleukin-10 Neurology Pharmacology/Toxicology Immunology Rheumatology Dermatology Allergology
Content Type	Text
Resource Type	Article
Subject	Pharmacology Immunology

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